The Experimental Study Of Molecular Immunological Mechanism About TGCO Against Rheumatoid Arthritis

The experimental study of molecular immunological mechanism about TGCO against rheumatoid arthritisAbrstractRheumatoid arthritis is a common systemic disease characterised by chronic joint inflammation, degradation of the extracellular matrix and destruction of the architecture and function of joint. Histoolgicaily, hyperplasia of the synovial lining cells, an inflammatory cell infiltrate composed of lymphocytes and histiocytes with scattered plasma cells and granulocytes and destructive changes of connective tissue and cartilage are seen. In order to provide the experimental basis for adjuvant arthritis (AA) and clinical use of chinese new herb of total glycosides from Cornus Officinalis(TGCO) capsule. We have establisted the niurine model of AA to research the detailed molecular immunological mechanism for TGCO.l.Effects of prevention and cure of TGCO on AAWe have succesefiully establisted the murine model of AA to research effects of prevention and cure of TGCO .The results showed that TGCO had the well effect of prevention and cure on AA. TGCO could inhibit joints of the forepart primary and secondary affect swell. TGCO could inhibit hyperplasia of the synovial lining cells, an inflanunatory cell infiltrate and destructive changes of connective tissue and cartilage of joints of the secondary affect pathology.2.The study of molecular immunological mechanism about TGCO against AAOn the basis of above, we have investigated the molecular immunological mechanism about TGCO against AA. The experimental results showed that TGCO could suppress the proliferation of T lymphocytes stimulated with ConA and DTH reaction in rats adjuvant arthritis. It had the inhibitory effect on IL-i ,IL-6 and TNFa produced in cultured peritoneal macrophages and PEG2 in plasma in rats adjuvant arthritis. It had the inhibitory effect on iNOSmRNA gene expression and the induced effect on IL-ira mRNA gene expression in peritoneal macrophages of SD rats adjuvant arthritis in vivo. It had the inhibitory effect of differed concentration of TGCO on IL-6mRNA gene expression and iNOSmRNA gene expression in cultured rat peritoneal macrophages stimulated with LPS in vitro. The effects of TGCO on T lymphocytes and T lymphocytes subgroup, and the IL-2 production of T lymphocytes were studied in healthy mice in order to explore the immunosuppressive mechanism of TGCO. The results showed that all the different doses of TGCO could inhibit the multiplication of T lymphocytes, CD3 surfaceexpression in T lymphocytes, and CD4 and CD8 surface expression in T lymphocytes: besides, middle and large TGCQ doses could increase the ratio of CD4/CD8 which implies that the TGCO effect of inhibiting CD8 is stronger than that of inhibiting CD4. The results also showed that all the different doses of TGCO could inhibit the IL-2 production of I lymphocytes.TGCO could inhibite the expression of adhesion molecules(ICAM-l and CD~) and integrin (a 4 ~ 7)with cytokines (IL-I and TNF- a )st駈ulated ECV3O4 in vitro that is an immortal endothelial cell line derived from HUVEC.We conclude that total glycosides of comus officinalis (TGCO) were extract from cornus officinalis of an Chinese herb have immunosuppressive effects and against rats adjuvant arthritis. It is the main molecular immunological mechanism of against rats adjuvant arthritis that suppressed function of cell immune and inhibited the expression of adhesion molecules(ICAM-l and CD~) and integrin (a 4 ~ 7) and had inhibitory effect on IL-l,IL--6 and TNF- a produced and iNOSmRNA gene expression and induced effect on IL-ira mRNA gene expression in cultured peritoneal macrophages of SD rats adjuvant arthritis.